tbuckley/cabot-search huggingface dataset:
PD-1 inhibitors combined with apatinib for advanced diffuse gastric cancer: A retrospective study.
Authors: Beibei Chen, Huichen Zhao, Saiqi Wang, Huifang Lv, Weifeng Xu, Caiyun Nie, Jianzheng Wang, Jing Zhao, Yunduan He, Xiaobing Chen
Journal: Journal of Clinical Oncology (2022)

e16009 Background: Numerous studies have shown that immunotherapy has a synergistic effect when combined with targeted drug therapy. Apatinib has been proven effective in advanced gastric cancer. Based on these facts and to assess the efficacy and safety of programmed death 1 (PD-1) inhibitors and apatinib as combination therapy in patients (pts) with unresectable locally advanced or metastatic diffuse gastric cancer(DGC), a retrospective clinical research study was carried out. Methods: Retrospective analysis of a cohort of pts with advanced diffuse gastric cancer received treatment of apatinib combined with PD-1 inhibitors enrolled in our institution between January 2019 and January 2021.Pts (n = 34) received PD-1 inhibitors and apatinib (250mg once daily) in this retrospective study. Overall survival (OS) and progression free survival (PFS) were estimated by Kaplan Meier curves, and other endpoints included objective response rate(ORR), disease control rate(DCR), prognostic factors. Results: A total of 34 pts were enrolled in a real-world dataset from Henan Cancer Hospital. 2 pts achieved partial response(PR),17 pts had stable disease(SD),and 15 pts had progressive disease (PD). The ORR and DCR were 5.88% (2/34) and 55.88% (19/34), respectively. The median PFS(mPFS) was 2.47 months (95%CI:1.9-3.0), and the median OS (mOS) was 6.80 months (95%CI 3.7-9.9). Pts with less than 3 metastatic sites had longer mOS than those with more metastatic sites(2.70 vs. 7.73 P &lt; 0.05). And in this study, the levels of platelet, albumin, CEA, CA199, CA125 and LDH affect patients’ prognosis. Kaplan-Meier analyses revealed that patients with normal platelet had better mOS than those with higher platelet(mOS 7.10 vs 0.3; P &lt; 0.05).And similar results were found in the pts with normal albumin. The mOS of those was longer than the pts with lower or higher albumin(7.73 vs 2.20 vs 2.53, P &lt; 005). And we demonstrated that positive groups of CEA(&gt; 4.7ng/ml), CA125(&gt; 35U/ml), CA199(&gt; 27U/ml) and LDH(&gt; 245U/L) were significantly associated with worse outcomes than that of negative groups(all P &lt; 0.05). The incidence of grade 3 or 4 treatment-related adverse events (TRAEs) was 26.5%(9/34). These adverse events (AEs) included pruritus, rash, hand-foot syndrome, hypertension and increased aspartate aminotransferase (AST) or alanine aminotransferase (ALT). No treatment-related deaths occurred. Conclusions: Combination therapy of PD-1 inhibitors and apatinib showed encouraging clinical activity and demonstrated tolerable toxicity in pts with advanced DGC. The level of platelet, albumin, CEA, CA199, CA125 and LDH could predict the prognosis of DGC patients.
A next generation inducible armored CAR to overcome the immunosuppressive tumor microenvironment and enhances cytotoxicity of CAR-T and TILs.
Authors: David Granger, Micaela Harrasser, Rachel Evans, Vincent Muczynski, Kerry Chester, Amit C. Nathwani
Journal: Journal of Clinical Oncology (2022)

e14517 Background: The full potential of CAR-T cells in clinic is limited by the immunosuppressive tumour microenvironment (TME), which induces expression of exhaustion markers and limits the activity of tumour infiltrating lymphocytes (TILs) including CAR-T cells. We developed a next generation inducible Armored CAR platform (aCAR) that releases an anti-PD-1 checkpoint inhibitor upon CAR-T cell activation, limiting payload release exclusively to the TME, thereby reducing the risk of systemic exposure. This differentiated strategy facilitates activation of CAR-T cells and TILs within the TME and has the potential for lower toxicity. Methods: A ROR1-targeting second-generation CAR containing a 41BB-CD3ζ intracellular domain was cloned into a lentivirus transfer vector alongside a prototypic anti-PD1 antibody. The CAR was under the control of a constitutively active promoter, and the PD1 targeting payload was controlled by an inducible promoter that was activated upon engagement of CAR with ROR1 on tumour cells. CAR-T cells were subject to in vitro co-culture assays with target ROR1 + tumour cells and their cytotoxic responses evaluated by flow cytometry. Levels and binding functionality of released payload were analyzed by ELISA and flow cytometry. In vivo xenograft models were performed in NSG mice with tumor growth assessed by bioluminescent imaging (BLI) and caliper measurement of the tumour volume. Results: Non-Armored CAR cells displayed potent and specific cytotoxic responses directed towards ROR1 + TNBC and NSCLC cells lines at different effector to target (E:T) ratios. The results were equivalent or superior to CARs generated with comparator anti-ROR1 antibodies, which may be due to the ROR1 CAR targeting a membrane proximal epitope within the ROR1 frizzled domain. The aCAR cells released measurable levels of anti-PD1 payload within 5 hours of binding to ROR1 on tumors and enhanced the cytotoxic effects at challenging 1:10 E:T ratios. Established PDL1 + TNBC xenograft models using the aCAR cells and comparing with non-Armored CAR cells displayed a qualitative abrogation in tumor growth by BLI, which was confirmed and shown to be significant by caliper measurement of the tumor volume. Continuing the experiment out to 3 months showed a significant survival advantage for the animals receiving aCAR. All other cohorts were terminated by day 70, however 20% of the aCAR cohort survived at day 95. Conclusions: Our next generation inducible aCAR platform enables the release of an immune stimulating payload only in the presence of target tumor cells, enhancing the therapeutic activity of the CAR-T cells and limiting payload exposure to the site of action. This technology provided a significant survival advantage in challenging in vivo xenograft models. This coupled with its potential safety attributes merits further clinical evaluation of this approach.
A randomized phase III clinical trial of acupuncture for chemotherapy-induced peripheral neuropathy (CIPN) in cancer survivors.
Authors: Andee Dooley, Katherine Han, Wanqing Iris Zhi, Lauren Piulson, Christina Seluzicki, Ting Bao
Journal: Journal of Clinical Oncology (2022)

TPS12145 Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a common and debilitating side effect in cancer survivors that can last long after completion of neurotoxic chemotherapy. Patients with CIPN often experience neuropathy symptoms such as pain, tingling, numbness, paresthesia, and dysesthesia, which can lead to significant functional decline and diminished quality of life (QoL). Our prior study showed that more than half of breast cancer survivors who received taxane-based chemotherapy experienced persistent peripheral neuropathy symptoms for a mean duration of 5.6 years after completing chemotherapy. This outcome highlights the importance of developing effective CIPN treatments to improve cancer survivors’ QoL. Identifying nonpharmacological approaches to reduce CIPN symptoms and improve cancer survivors’ outcomes is urgently needed. Acupuncture is a widely used, minimally invasive Traditional Chinese Medicine technique that has shown promising evidence as an effective and safe treatment for CIPN. We hypothesize that acupuncture may reduce CIPN pain and improve overall CIPN symptoms in cancer survivors. Methods: We are conducting a two-arm, parallel randomized clinical trial comparing electroacupunture (EA) versus sham acupuncture (SA) in cancer survivors at Memorial Sloan Kettering Cancer Center, New York, NY. The EA arm includes a total of ten sessions of EA over eight weeks using a standardized, semi-fixed protocol developed by our group based on the previously published pilot study (NCT03183037). The SA arm includes a sham technique that uses a combination of non-acupuncture points and a non-insertion procedure in ten sessions over eight weeks. The primary outcome of this study is the Brief Pain Inventory-Short Form (BPI-SF) average pain item. The secondary outcomes are quantitative sensory testing measures and additional patient-reported outcomes that include the BPI-SF pain interference subscale, Neuropathic Pain Scale (NPS), Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-Ntx), CIPN-20, PROMIS Global Health Scale, and Patients’ Global Impression of Change (PGIC). The primary end point is week 12 and the secondary end point is week 24; treatment effects are assessed at baseline and at weeks 4, 8, 12, 18, and 24. Eligibility criteria includes: 1) Moderate-to-severe CIPN pain, defined by a score of 4 or greater on a 0–10 numeric rating scale; 2) completion of neurotoxic chemotherapy at least three months prior to enrollment; and 3) no changes in anti-neuropathy medications within three months of enrollment. We have accrued 30 participants as of February 2022, with a total accrual target of 250 participants. Accrual completion is anticipated by December 2024. Funding resource: NIH R37 CA248563. Clinical trial information: NCT04917796.
Publisher Correction: Dual function NFI factors control fetal hemoglobin silencing in adult erythroid cells
Authors: Kunhua Qin, Peng Huang, Ruopeng Feng, Cheryl A. Keller, Scott A. Peslak, Eugene Khandros, Megan S. Saari, Xianjiang Lan, Thiyagaraj Mayuranathan, Phillip A. Doerfler, Osheiza Abdulmalik, Belinda Giardine, Stella T. Chou, Junwei Shi, Ross C. Hardison, Mitchell J. Weiss, Gerd A. Blobel
Journal: Nature Genetics (2022)
Avoiding renorraphy at the end of off-clamp robotic partial nephrectomy does not jeopardize surgical and functional outcomes: A single center analysis
Authors: A. Brassetti, U. Anceschi, A. Bove, M. Costantini, M.C. Ferriero, S. Guaglianone, R. Mastroianni, L. Misuraca, G. Tuderti, G. Simone
Journal: European Urology (2022)
Tiragolumab Results Cast Shadow on TIGIT Pipeline
Journal: Cancer Discovery (2022)

Abstract Genentech's TIGIT-targeted antibody tiragolumab missed its endpoints in two late-stage lung cancer trials, raising doubts about one of the most widely studied next-generation checkpoint targets in immuno-oncology. But numerical signs of benefit among certain patients with metastatic non–small cell lung cancer suggest that TIGIT blockade still has potential—if drug developers can successfully identify the best indications, drug combinations, or patient populations.
Peer-to-peer counseling in non-metastatic prostate cancer: Results from a randomized controlled trial
Authors: J. Huber, P. Karschuck, R. Koch, A. Ihrig, T. Krones, A. Neisius, S. Von Ahn, C. Klopf, S. Weikert, M. Siebels, N. Haseke, C. Weißflog, M. Baunacke, P. Liske, G. Tosev, T. Benusch, M. Schostak, J. Stein, P. Spiegelhalder, C. Thomas, C. Groeben
Journal: European Urology (2022)
Lurbinectedin in patients with pretreated<i> BRCA</i>1/2-associated metastatic breast cancer: Results from a phase II basket study.
Authors: Valentina Boni, Barbara Pistilli, Irene Brana, Geoffrey Shapiro, Jose Manuel Manuel Trigo Perez, Victor Moreno, Daniel E. Castellano, Cristian Marcelo Fernandez, Carmen Maria Kahatt, Vicente Alfaro, Mariano Siguero, Ali Hassan Zeaiter, Federico Longo, Khalil Zaman, Antonio Antón Torres, Alfredo Paredes Lario, Gerardo Huidobro Vence, Vivek Subbiah
Journal: Journal of Clinical Oncology (2022)

1092 Background: Lurbinectedin (L) is a selective inhibitor of oncogenic transcription that leads to cell apoptosis and shows antitumor activity against homologous recombination repair-deficient cell lines. A previous phase II study (Cruz et al. JCO 2018;36:3134-3143) demonstrated antitumor activity in patients (pts) with pretreated metastatic breast cancer (median of 1 prior advanced chemotherapy line) and BRCA1/2-mutated tumors with L 3.5 mg/m 2 or 7.0 mg flat dose (equivalent to 4.0 mg/m 2 ) every three weeks [q3wk]). This report focuses on the outcomes in the BRCA1/2-associated breast cancer cohort of a phase II Basket multitumor trial. Methods: This phase II study evaluated L 3.2 mg/m 2 1-hour intravenous (i.v.) infusion q3wk in a cohort of 21 female pts with pretreated BRCA1/2-associated breast cancer. The primary efficacy endpoint was ORR according to RECIST v1.1. Secondary endpoints included duration of response (DoR), progression-free survival (PFS), OS and safety. Results: Median age was 45 years (range, 29-73 years). Hormone receptor (HR)+ disease was observed in 76.2% of pts, triple negative disease in 19.0% and HER2+ in 9.5%. BRCA1 and BRCA2 were reported in 47.6% and 52.4% of pts, respectively. Median number of prior lines of chemotherapy for advanced disease was 2 (range, 0-3 lines). Prior poly(ADP-ribose) polymerase inhibitors and platinum compounds had been administered to 23.8% and 47.6% of pts, respectively. Confirmed partial response (PR) was observed in six pts (ORR = 28.6%; 95% CI, 11.3-52.2%). Lurbinectedin was active in both BRCA mutations: four PRs in 11 pts (36.4%) in BRCA2 and two PRs in 10 pts (20.0%) in BRCA1. Median DoR was 8.6 months, median PFS was 4.1 months and median OS was 16.1 months. Stable disease (SD) was observed in ten pts (47.6%), including three pts with unconfirmed response in a subsequent tumor assessment (ORR unconfirmed = 42.9% [95%CI, 21.8-66.0]). Clinical benefit rate (PR + SD≥4 months) was 76.2% (95% CI, 52.8-91.8%). The most common grade 3/4 toxicity was neutropenia (42.9%; grade 4, 23.8%; with no febrile neutropenia). Conclusions: This phase II study met its primary endpoint and confirmed the activity of L in pretreated BRCA1/2-associated breast cancer pts. L 3.2 mg/m 2 1-hour i.v. infusion q3wk showed an acceptable, predictable and manageable safety profile. Considering the exploratory aim of this trial as well as previous results in other phase II study, further development of L in this indication is warranted. Clinical trial information: NCT02454972.
Brain 18-FDG-PET patterns in early breast cancer subtypes: Relationship with headache.
Authors: Rita De Sanctis, Lidija Antunovic, Chiara Benvenuti, Flavia Jacobs, Mariangela Gaudio, Mariya Ilieva, Alessandro Viganò, Arturo Chiti, Armando Santoro
Journal: Journal of Clinical Oncology (2022)

e12560 Background: Brain metabolic response on 18F-fuorodeoxiglucose(FDG)-PET in breast cancer (BC) patients is not routinely investigated, although several bidirectional relationships have been described between BC (and BC therapies) and brain functions. For example, common forms of headaches, as migraine (Mi) and tension-type headache (TTH), seem to be oddly distributed among BC subtypes and possibly influence the outcome. Methods: We recruited patients with early BC referring to IRCCS Humanitas Research Hospital who received neoadjuvant chemotherapy. Demographic data, BC characteristics and headache diagnosis were recorded, through detailed interview and instrumental investigation. Ki67 was considered high if above 20%. All patients underwent dedicated 18F-FDG PET scan for the evaluation of brain metabolism. Semiquantitative image analysis was performed using Cortex ID software (GE), comparing patient’s scan with a control group by the means of Z-score. The difference between patients’ subgroups were assessed using One-way ANOVA model. Results: Twenty-three patients were recruited. The median age was 52.5±10.8 years; 65.2% were postmenopausal, 30% premenopausal, and one patient perimenopausal. Ten patients were diagnosed as triple-negative BC, 6 as HER2-positive and 7 as Luminal B/HER2+. Nearly 70% (16/23) of patients had high Ki67 values. All patients had ECOG PS 0. Ten patients were diagnosed with TTH, 9 with migraine of whom two with aura, and four patients had no headache. Eleven patients had active headache at the moment of the study. At the whole brain level, we found a significant increase of brain metabolism in the left hemisphere of BC patients with high Ki-67 (p=0.007). Moreover, the same result was found in parietal cortex and in general associative areas bilaterally. Instead, HER-2 positive BC patient showed a reduced metabolism in right temporal cortex compared to HER-2 negative (p=0.04). Grading and other tumor characteristics did not influence FDG-PET uptake. BC patients with TTH had a reduced activity in right medial frontal lobe compared with migraine patients (p=0.01). Those with an active headache had increased activity in posterior cingulate and reduced activity in visual networks (p=0.03). Conclusions: Although exploratory, this study suggests that BC subtypes could present different metabolic pattern of cerebral activity, particularly in dominant hemisphere and associative areas. The high prevalence of headache in our sample does not affect the above pattern, but it is associated with an altered activation in other networks, mainly cingulate and visual cortex, which are well-known areas involved in primary headache.
Diurnal Variation in thrombolytic status in patients presenting with STEMI
Authors: Y X Gue, M Farag, N Spinthakis, D Wellsted, D Gorog
Journal: Cardiovascular Research (2022)

Abstract Funding Acknowledgements Type of funding sources: None. Background Prior studies mainly in healthy volunteers and patients with stable coronary artery disease (CAD) indicate circadian variation in spontaneous fibrinolytic activity. This is predominantly attributable to changes plasminogen activator inhibitor-1 (PAI-1) levels peaking between midnight and 06:00 hr, with a nadir at 18:00 hr. Whether circadian variation in spontaneous fibrinolysis exists amongst patients with ST-elevation myocardial infarction (STEMI) is unknown. Purpose It was our aim to assess circadian variation in fibrinolytic status in the acute setting in patients presenting with STEMI. Methods A prospective, observational study was conducted in patients presenting with STEMI for primary percutaneous coronary intervention (PPCI). Blood was tested on arrival pre-PPCI, after aspirin and P2Y12 inhibitor administration, but before any anticoagulant or antithrombotic agent administration in the cardiac cath lab. Venous blood was assessed to determine endogenous fibrinolysis using the Global Thrombosis Test, which utilises non-anticoagulated blood to assess the formation of an occlusive thrombus under high shear and the time taken for spontaneous restart of flow as a measure of endogenous fibrinolysis (lysis time, LT). Results A total of 527 patients were included, aged 64±13 years and 78% were male. 304 (58%) patients presented within working hours (08:00-17:00) with peak presentation between 11:00-12:00 and trough between 03:00 to 05:00 hrs. Lysis time was not related to time of presentation. Time of presentation was divided into 4 groups (A 00:00-05:59, B 06:00-11:59, C 12:00-17:59, D 18:00-23:59 hrs). There was no significant difference in LT between patients presenting at the 4 timepoints (median 1362s [interquartile range IQR 1077-1808] vs 1503s [1182-2056] vs 1440s [1164-1998] vs. 1420s [1125-1820], respectively, p=0.340). When comparing Group A to C, the LT was not significantly different (1362s [1077-1808] vs. 1440 [1164-1998], p=0.413). The presentation time of patients with impaired endogenous fibrinolysis (LT&amp;gt;3000 sec) did not differ significantly from patients with normal endogenous fibrinolysis. The hourly variation was similar in diabetics and non-diabetics, but the variation in lysis time appeared blunted in patients taking long term aspirin prior to presentation compared to non-aspirin takers. Conclusion In contrast to the known circadian variation in fibrinolysis in normal volunteers, and stable CAD, in our large cohort of STEMI patients, there appears to be no relationship between time of presentation/onset of STEMI and the effectiveness spontaneous fibrinolysis. This is reflected in our observation, supported by most contemporary studies, that peak time of STEMI presentation is during the late morning, and this does not relate to known circadian variation in fibrinolysis markers in CAD.
Urethral stricture following endoscopic prostate surgery: A systematic review and meta-analysis of prospective, randomized trials
Authors: G.M. Pirola, V. Gauhar, E. Rubilotta, M.L. Wroclawski, D.L.Q. Nguyen, M. Gubbiotti, E.J. Lim, V.W. Chan, M. Corrales, E. Garcia Rojo, T.R.W. Herrmann, J.Y-C. Teoh, D. Castellani
Journal: European Urology (2022)
Interruption of imatinib in advanced gastrointestinal stromal tumor after prolonged imatinib maintenance in the absence of gross tumor lesions.
Authors: Yoon-Koo Kang, Hyung-Don Kim, Hyun Jin Kim, Young Soo Park, Moyeol Beck, Min-Hee Ryu
Journal: Journal of Clinical Oncology (2022)

11539 Background: Although current guidelines recommend indefinite imatinib treatment in advanced gastrointestinal stromal tumor (GIST) patients, prolonged imatinib treatment is often challenging. Imatinib-refractory progression-free survival (PFS) and overall survival were reportedly not different between those who interrupted imatinib and those did not. Methods: Clinical outcomes of 77 consecutive patients with recurrent or metastatic GIST who interrupted imatinib treatment after maintaining around 5 years of imatinib treatment in the absence of gross tumor lesions were retrospectively analyzed. Association between clinical factors and progression-free survival (PFS) following imatinib interruption was analyzed. Results: Median time from the absence of gross tumor lesions to imatinib interruption was 61.5 months (range 41.4–122.7 months). Since imatinib interruption, median PFS was 19.6 months, and the PFS rate at 60 months was 26.3%. Among patients who had progressive disease following interruption, imatinib re-introduction led to 88.6% objective response rate and 100% disease control rate, with the median imatinib-refractory PFS since re-introduction of 112.4 months. Complete removal of initial gross tumor lesion(s) (hazard ratio [HR] 0.32, 95% confidence interval [CI] 0.12–0.81, P = 0.016) and complete removal of residual gross tumor lesion(s) (HR 0.45, 95% CI 0.21–0.94, P = 0.033) by local treatment (vs. no local treatment or residual lesions after local treatment) were independently associated with favorable PFS. Conclusions: Interruption of imatinib may be considered with close surveillance in selected patients who maintained years of imatinib treatment in the absence of gross tumor lesions, especially for those who had complete removal of gross tumor lesions by local treatment.
The effectiveness and patient tolerability of urologic procedures conducted under conscious sedation
Authors: A. Pierce, K. Panchendrabose, N.T. Gebru, R. Grewal, K. Jain, R. Blachman-Braun, E. Saltel, B. Peters, R. Bard, J. Saranchuk, P. Patel
Journal: European Urology (2022)
Prospective multicentre long-term analysis of oral morbidity after oral mucosa grafts harvesting for substitution or augmentation urethroplasties
Authors: E. Fernández Guzman, J. Ponce De León Roca, J.L. Lozano Ortega, M. Arrabal Martin, E. Fernández Pascual, I. Povo Martin, A. Restrepo-González, J. Medina Polo, A. Sabio Bonilla, M. Pascual Samaniego, E. Morán Pascual, J.M. Gonzalez Suarez, P. Calleja-Hermosa, F. Campos-Juanatey
Journal: European Urology (2022)